Apoptosis or programmed cell death is an important physiological process in multicellular organisms, both during development and for homeostasis. Apoptosis allows the elimination of cells that are no longer necessary, that are produced in excess, that have developed improperly or that have sustained genetic damage. Apoptosis occurs in many different tissue systems and must be properly regulated to maximize benefit to the individual; when the mechanism is dysregulated, it may cause significant disease. Both inhibition of cell death and inappropriate cell death may be deleterious. For example, inhibition of cell death may contribute to disease in the immune system to allow persistence of self-reactive B and T cells, thus promoting autoimmune disease (Watanabe-Fukunaga et al., Nature, 356:314-317 (1992)). Most importantly, cancer may result when cells that fail to die undergo further mutations, leading to a transformed state (Korsmeyer, S. J., Blood, 80:879-886 (1992)).
The protein, Fas, mediates apoptosis. A cell surface receptor, Fas plays an important role in the development and function of the immune system. Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases. Exacerbation of Fas-mediated apoptosis may cause tissue destruction.